Jean-Christophe Leroux

Last Name

Leroux

First Name

Jean-Christophe

ORCID

0000-0001-5601-1292

Organisational unit

03811 - Leroux, Jean-Christophe / Leroux, Jean-Christophe

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Publications 1 - 10 of 213

Photopolymerization Inks for 3D Printing of Elastic, Strong, and Biodegradable Oral Delivery Devices
Yuts, Yulia; Bohley, Marilena; Krivitsky, Adva; et al. (2024)
Advanced Functional Materials
Three-dimensional (3D) printing via vat photopolymerization is transforming the manufacturing paradigms of biomedical devices, offering tremendous advantages for the production of customized advanced drug delivery systems. However, the existing commercial inks often lack the ability to simultaneously provide elasticity, strength, and biodegradability. Herein, photopolymerizable inks based on poly(β-aminoester) diacrylates and N-vinyl pyrrolidone are used to address these limitations. These biodegradable polymers enable the digital light processing 3D printing of elastomers with adjustable elongation at break (103–762%), stress at failure (0.2–8.3 MPa), and hydrolysis rates ranging from 25 min to 80 days. The authors are able to synthesize a soft polymer that possess properties akin to natural latex, which can enhance its elastic modulus when subjected to high strains. It can withstand 762% stretch with a maximum strength of 8.3 MPa. In addition, this polymer demonstrates cytocompatibility and unique biodegradation properties under simulated gastrointestinal conditions (within hours at pH 6.8). By utilizing this elastomer, a prototype of an expandable oral drug delivery device that has the ability to degrade within the average transit time in the jejunum is manufactured. This study paves the way to leverage vat photopolymerization 3D printing in the creation of complex prototypes of biomedical devices where strength, elasticity and biodegradability are essential.
Permeation of steryl ferulates through an in vitro intestinal barrier model
Zhu, Dan; Brambilla, Davide; Leroux, Jean-Christophe; et al. (2015)
Molecular Nutrition & Food Research
A Degradable Device for Sustainable Capillary Blood Sampling
Zoratto, Nicole; Krupke, Hanna; Mantella, Valeria; et al. (2025)
Advanced Materials Technologies
Capillary blood sampling plays a crucial role in diagnostic decentralization, yet most microsampling devices remain expensive, limiting their use mainly to developed countries. To improve accessibility, a cost‐effective silicone device capable of extracting small volumes of capillary blood in vivo was previoulsy developed by our group. However, the use of non‐degradable materials poses limitations, especially in resource‐limited settings with inadequate waste disposal infrastructure. Herein, a nearly fully degradable microsampling prototype is reported. The device body is fabricated using digital light processing 3D printing with tailored poly(ɛ‐caprolactone‐co‐D,L‐lactide). This device yields negative pressure and adhesion strength comparable to the original prototype, although it requires greater manual compression. In vitro, it collects ≈670 µL of porcine whole blood, matching the volume drawn by the silicone counterpart. The device is equipped with magnesium microneedle blades coated with poly(ɛ‐caprolactone) to enhance blood stability. Degradation studies show complete disintegration of poly(ɛ‐caprolactone‐co‐D,L‐lactide) under composting conditions within 60 days, and near‐complete degradation of magnesium blades in aqueous buffer within 40 days. Preliminary hemolysis assays confirm blood compatibility of both the 3D‐printed device and coated microneedles, with sample quality preserved for up to 3 h. Altogether, these findings highlight the potential of this degradable prototype as a sustainable alternative for capillary blood collection.
Biomedical applications of bisphosphonates
Giger, Elisabeth V.; Castagner, Bastien; Leroux, Jean-Christophe (2013)
Journal of Controlled Release
Improving extracellular vesicles production through a Bayesian optimization-based experimental design
Bader, Johannes; Narayanan, Harini; Arosio, Paolo; et al. (2023)
European Journal of Pharmaceutics and Biopharmaceutics
With the growing demand and diversity of biological drugs, developing optimal processes for their accelerated production with minimal resource utilization is a pressing challenge. Typically, such optimization involves multiple target properties, such as production yield, biological activity, and product purity. Therefore, strategic experimental design techniques that can characterize the parameter space while simultaneously arriving at the optimal process satisfying multiple target properties are required. To achieve this, we propose the use of a multi-objective batch Bayesian optimization (MOBBO) algorithm and illustrate its successful application for the production of extracellular vesicles (EVs) from a 3D culture of mesenchymal stem cells (MSCs) considering three objectives, namely to maximize the vesicle-to-protein ratio, maximize the enzymatic activity of the MSC-EV protein CD73, and minimize the amount of calregulin impurities. We show that the optimal combination of the process parameters to address the intended objectives could be achieved with only 32 experiments. For the four parameters considered (i.e., microcarrier concentration, seeding density, centrifugation time, and impeller speed), this number of experiments is comparable to or lower than the classical design of experiments (DoE) and the traditional one-factor-at-a-time (OFAT) approach. We illustrate how the algorithm adaptively samples in the process parameter space, selectively excluding unfavorable regions, thus minimizing the number of experiments required to reach optimal conditions. Finally, we compare the obtained solutions to the literature data and present possible applications of the collected data for other modeling activities such as Quality by Design, process monitoring, control, and scale-up.
Transport of CLCA2 to the nucleus by extracellular vesicles controls keratinocyte survival and migration
Seltmann, Kristin; Hettich, Britta; Abele, Seraina; et al. (2024)
Journal of Extracellular Vesicles
Chloride channel accessory 2 (CLCA2) is a transmembrane protein, which promotes adhesion of keratinocytes and their survival in response to hyperosmotic stress. Here we show that CLCA2 is transported to the nucleus of keratinocytes via extracellular vesicles. The nuclear localization is functionally relevant, since wild-type CLCA2, but not a mutant lacking the nuclear localization signal, suppressed migration of keratinocytes and protected them from hyperosmotic stress-induced cell death. In the nucleus, CLCA2 bound to and activated β-catenin, resulting in enhanced expression of Wnt target genes. Mass-spectrometry-based interaction screening and functional rescue studies identified RNA binding protein 3 as a key effector of nuclear CLCA2. This is of likely relevance in vivo because both proteins co-localize in the human epidermis. Together, these results identify an unexpected nuclear function of CLCA2 in keratinocytes under homeostatic and stress conditions and suggest a role of extracellular vesicles and their nuclear transport in the control of key cellular activities.
The intracellular journey of DNA delivered with the protein-based transfection system TFAMoplex and Lipofectamine
Greitens, Christina; Honrath, Steffen; Maurer, Philip; et al. (2025)
International Journal of Pharmaceutics
In non-viral DNA delivery, assessing the cellular trafficking of DNA is crucial to understand how transfection systems interact with the cellular machinery. Using a combination of innovative and established imaging assays and flow cytometry, we characterize DNA delivery in HeLa cells with three different transfection systems: (i) the original protein-based TFAMoplex, using the mitochondrial transcription factor A (TFAM) for DNA compaction, (ii) a modified version of the TFAMoplex incorporating a basic leucine zipper (bZIP) domain, (TFAMoplex-bZIP), and (iii) Lipofectamine. Particularly, DNA cell association, uptake, endosomal rupture, cytoplasmic delivery and reporter gene expression are assessed. TFAMoplex-bZIP mediated delivery of Cy3-labeled DNA shows significantly higher cell association compared to the original TFAMoplex and Lipofectamine (15.6, 6.6. and 0.53 Cy3 objects per cell, respectively). However, the highest DNA internalization efficiency is achieved with Lipofectamine (21.8 % vs. ∼15 % for TFAMoplex-based systems). All transfection systems induce endosomal rupture and the formation of barrier-to-autointegration factor (BAF)-positive nucleoprotein structures, termed BAF clusters. With TFAMoplex-bZIP, BAF clusters are numerous, and significantly more cells show reporter gene expression (46.7 %) compared to Lipofectamine (8.7 %). However, reporter protein intensity is highest with Lipofectamine. The described high-precision characterization tools of DNA delivery might be applied to other non-viral transfection agents to identify their bottlenecks in detail.
The intracellular visualization of exogenous DNA in fluorescence microscopy
Greitens, Christina; Leroux, Jean-Christophe; Burger, Michael (2024)
Drug Delivery and Translational Research
In the development of non-viral gene delivery vectors, it is essential to reliably localize and quantify transfected DNA inside the cell. To track DNA, fluorescence microscopy methods are commonly applied. These mostly rely on fluorescently labeled DNA, DNA binding proteins fused to a fluorescent protein, or fluorescence in situ hybridization (FISH). In addition, co-stainings are often used to determine the colocalization of the DNA in specific cellular compartments, such as the endolysosomes or the nucleus. We provide an overview of these DNA tracking methods, advice on how they should be combined, and indicate which co-stainings or additional methods are required to draw precise conclusions from a DNA tracking experiment. Some emphasis is given to the localization of exogenous DNA inside the nucleus, which is the last step of DNA delivery. We argue that suitable tools which allow for the nuclear detection of faint signals are still missing, hampering the rational development of more efficient non-viral transfection systems.Graphical abstract The intracellular visualization of exogenous DNA in fluorescence microscopy. Created with BioRender.com.
Efficient protein targeting to the inner nuclear membrane requires atlastin-dependent maintenance of ER topology
Pawar, Sumit; Ungricht, Rosemarie; Tiefenboeck, Peter; et al. (2017)
eLife
Newly synthesized membrane proteins are targeted to the inner nuclear membrane (INM) by diffusion within the membrane system of the endoplasmic reticulum (ER), translocation through nuclear pore complexes (NPCs) and retention on nuclear partners. Using a visual in vitro assay we previously showed that efficient protein targeting to the INM depends on nucleotide hydrolysis. We now reveal that INM targeting is GTP-dependent. Exploiting in vitro reconstitution and in vivo analysis of INM targeting, we establish that Atlastins, membrane-bound GTPases of the ER, sustain the efficient targeting of proteins to the INM by their continued activity in preserving ER topology. When ER topology is altered, the long-range diffusional exchange of proteins in the ER network and targeting efficiency to the INM are diminished. Highlighting the general importance of proper ER topology, we show that Atlastins also influence NPC biogenesis and timely exit of secretory cargo from the ER.
Pharmacokinetics of lipid-drug conjugates loaded into liposomes
Signorell, Rea D.; Luciani, Paola; Brambilla, Davide; et al. (2018)
European Journal of Pharmaceutics and Biopharmaceutics

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Jean-Christophe Leroux

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